Ni-catalysed assembly of axially chiral alkenes from alkynyl tetracoordinate borons via 1,3-metallate shift

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(1), P. 42 - 53

Published: Jan. 1, 2024

Language: Английский

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Pd-Catalyzed Asymmetric Larock Indole Synthesis to Access Axially Chiral N-Arylindoles

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(8), P. 5493 - 5501

Published: Feb. 13, 2024

Larock indole synthesis is one of the most straightforward and efficient methods for indoles; however, there has been no asymmetric version yet construction indole-based axially chiral N-arylindoles since its initial report in 1991. Herein we first example an by employing a sulfinamide phosphine (SadPhos) ligand (Ming-Phos) with palladium. It allows rapid wide range N-arylindole compounds good yields up to 98:2 er. The application this unique scaffold as organocatalyst promising. Furthermore, kinetic study revealed that alkyne migratory insertion rate-determining step, which proven density functional theory (DFT) calculations. Additionally, DFT studies also suggest N–C dihedral difference caused steric hindrance contributes enantioselectivity control.

Language: Английский

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Sadphos as Adaptive Ligands in Asymmetric Palladium Catalysis

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 31, 2024

ConspectusPalladium catalysis, as one of the most important strategies in asymmetric synthesis, has continuously attracted attention organic chemists. With development chiral ligands, increasingly challenging reactions and substantial progress catalysis are being realized.Since 2014, we have focused on exploiting a series sulfinamide phosphine ligands called "Sadphos," including Ming-Phos, Xu-Phos, Xiao-Phos, Xiang-Phos, TY-Phos, PC-Phos, GF-Phos, WJ-Phos. These can be easily prepared two to four steps using commercial materials. new types shown remarkable performance transition-metal-catalyzed reactions, especially Pd-catalyzed transformations. X-ray diffraction analysis, mechanistic studies, density functional theory calculations revealed that Sadphos coordinate with Pd0 PdII species Pd0/P, Pd0/P,S, or PdII/P,O modes.This Account summarizes our recent efforts toward palladium-catalyzed enantioselective ligands. were found privileged very crucial promote by increasing reactivity enantioselectivity. Ming-Phos is an effective ligand coupling intramolecular Heck providing highly trisubstituted allenes, axially anilides, gem-diarylmethine silanes, disubstituted dihydroisoquinolinones. Incorporation electron-rich cyclohexyl group moiety afforded which showed unique effect transformations, reductive Heck, dearomative Mizoroki–Heck, tandem Heck/Suzuki coupling, carboiodination, carboamination, cross-coupling reactions. Using similar strategy, synthesized more electron–rich TY-Phos Xiang-Phos bearing t-butyl 1-adamantyl at P atoms, respectively. Regarding stereoelectronic features, these characteristic best choice satisfy requirements fluoroarylation gem-difluoroalkenes, intermolecular α-arylation aldehydes, carboetherification alkenyl oximes, carboheterofunctionalization 2,3-dihydrofurans. Compared aforementioned attractive features high nucleophilicity originating from CH2PPh2 ortho-substituent side aryl ring, presumably responsible for its efficiency. The Pd/Xiao-Phos catalyst system shows good secondary oxides, affording P-stereogenic products multiple molecular skeletons. modification basic backbone introducing xanthene skeleton motivated us design synthesize monophosphines, named PC-Phos GF-Phos. various arylation sulfenate anions, denitrogenative cyclization benzotriazoles, dearomatization indoles. practicability GF-Phos was validated three-component N-tosylhydrazones, halides, terminal alkynes, well N-tosylhydrazones vinyl iodides pendent amines. In addition, ferrocene-derived WJ-Phos employed Suzuki–Miyaura reaction, biaryl monophosphine oxides excellent enantiomeric excesses.

Language: Английский

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Enantioselective Arylation of Sulfenamides to Access Sulfilimines Enabled by Palladium Catalysis

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(37)

Published: June 27, 2024

Abstract Sulfur‐containing functional groups have garnered considerable attention due to their common occurrence in ligands, pharmaceuticals, and insecticides. Nevertheless, enantioselective synthesis of sulfilimines, particularly diaryl sulfilimines remains a challenging persistent goal. Herein we report highly enantio‐ chemoselective cross–coupling sulfenamides with aryl diazonium salt construct diverse S(IV) stereocenters by Pd catalysis. Bisphosphine ligands bearing sulfinamide play crucial role achieving high reactivity selectivity. This approach provides general, modular divergent framework for quickly synthesizing chiral sulfoximines that are otherwise access. In addition, the origins chemoselectivity enantioselectivity were extensively investigated using density theory calculations.

Language: Английский

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Palladium-Catalyzed Allylic Alkylation Reactions of Nucleophilic Allenones: Asymmetric Allylic Alkylation, Z/E Divergent Allylic Alkylation, and [5 + 2] Annulation

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(13), P. 9940 - 9954

Published: June 19, 2024

Metal-catalyzed allenylic substitution reactions where allenes serve as electrophilic precursors have been recognized a rapid way for novel allene construction. On the contrary, chemistry in which act nucleophiles has far less investigated, especially powerful platform such metal-catalyzed allylic alkylation reactions. We herein describe two unprecedented palladium-catalyzed of an nucleophile. In first reaction, using vinyloxazolidinones allyl precursor, asymmetric allylation trisubstituted allenones worked well to prepare array axially chiral tetrasubstituted allenes. Mechanistic studies and density functional theory (DFT) calculations indicated that weak hydrogen-bonding interaction between acidic C(sp2)–H allenone nitrogen anion π-azaallyl-Pd species is key success stereocontrol. This reaction revealed intriguing reactivity nucleophilic time. second with use allenylethylene carbonates π-oxyallyl-Pd precursors, presented unique under different conditions provide divergent synthetic access (E)- (Z)-allenyl diene products. Interestingly, subsequent sequential intramolecular cyclization/isomerization (Z)-product delivered dihydrooxepine derivatives [5 + 2] annulation

Language: Английский

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Catalytic Asymmetric Synthesis of Sulfinamides via Cu-Catalyzed Asymmetric Addition of Aryl Boroxines to Sulfinylamines

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(26), P. 17580 - 17586

Published: June 20, 2024

The application of sulfinamides has been witnessed in medicinal and agrochemistry with employment asymmetric transformations. However, methods for their catalytic synthesis have rarely explored. Herein, the enantioselective addition aryl boroxines to sulfinylamines via Cu catalyst newly developed Xuphos ligand were reported. A series chiral can be readily accessed one step. This protocol enables stereospecific transformation sulfonimidoyl fluorides, sulfonimidamides, sulfonimidate esters. DFT calculations revealed reaction pathway, migratory insertion is enantio-determining noncovalent interaction between oxygen atom C-H bonds crucial enantioselectivity control.

Language: Английский

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Synthesis of Chiral Endocyclic Allenes and Alkynes via Pd-Catalyzed Asymmetric Higher-Order Dipolar Cycloaddition

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

A Pd-catalyzed asymmetric higher-order dipolar cycloaddition between allenyl carbonates and azadienes is achieved by exploiting novel alkylidene-π-allyl-Pd dipoles. This research provides a modular platform for the synthesis of challenging chiral endocyclic allenes bearing medium-sized heterocyclic motif centrally stereocenter in good yields with high enantio- diastereoselectivities (29 examples, up to 97% yield, 97:3 er >19:1 dr). Experimental computational studies elucidate possible reaction mechanism observed stereochemical results. Based on mechanistic understanding, new π-propargyl-Pd dipole was designed further extend success higher order strategy 10-membered alkynes from propargyl (13 98% yield 94.5:5.5 er).

Language: Английский

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Pd-Catalyzed Asymmetric Aza-Heck Cyclization/Sonogashira Reaction of Alkene-Tethered Oxime Esters and Alkynes

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(7), P. 5305 - 5313

Published: March 26, 2024

Over the past few decades, Narasaka–Heck-type difunctionalization of tethered alkenes has emerged as a powerful strategy to produce heterocyclic scaffolds. However, asymmetric synthesis rarely been explored. Herein, we report robust palladium-catalyzed enantioselective Narasaka–Heck cyclization–Sonogashira reaction alkene-tethered oxime esters and terminal alkynes. By employing new Ming-Phos ligand, obtain high yields pyrrolines with quaternary stereocenter enantioselectivities under mild conditions. Density functional theory (DFT) study reveals weak interaction between aromatic ring substrate fragment naphthyl group in which probably accounts for stereoselectivity.

Language: Английский

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SadPhos Library: A Comprehensive Resource for Exploring Chiral Ligand Chemical Space

Chemistry - An Asian Journal, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Abstract Traditionally, the discovery of ligands for organic reactions has relied heavily on intuition and experience chemists, leading to a trial‐and‐error process that is both time‐consuming inherently biased. The rise data science now offers more systematic efficient approach exploring chemical spaces, moving beyond heuristic constraints conventional ligand design enabling data‐driven, predictive method. In this study, we introduce “SadPhos Library”, comprehensive collection 890 reported chiral sulfinamide phosphine ligands, use physical descriptors systematically map their space. By examining small dataset known active demonstrate how SadPhos library can help identify key properties associated with performance thus streamline optimization. Furthermore, employing dimensionality reduction clustering techniques, pinpoint representative subset facilitates targeted exploration diverse landscape.

Language: Английский

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Enantioselective Palladium-Catalyzed Cascade Narasaka–Heck Cyclization/Suzuki Coupling Reaction

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 2516 - 2521

Published: Jan. 27, 2025

Language: Английский

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